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. 2024 Jul;31(35):48758-48772.
doi: 10.1007/s11356-024-34421-4. Epub 2024 Jul 23.

Involvement of aryl hydrocarbon receptor in the aflatoxin B1 and fumonisin B1 effects on in vitro differentiation of murine regulatory-T and Th17 cells

Verónica Sofía Mary  1 , Pilar Andrea Vélez  1 , Sol Quiroz  1 , Ignacio Beccacece  1 , Santiago Nicolás Otaiza-González  1 , Laura Silvina Chiapello  1 , Héctor Ramón Rubinstein  1 , Martín Gustavo Theumer  2
Affiliations

Involvement of aryl hydrocarbon receptor in the aflatoxin B1 and fumonisin B1 effects on in vitro differentiation of murine regulatory-T and Th17 cells

Verónica Sofía Mary et al. Environ Sci Pollut Res Int. 2024 Jul.

Abstract

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely found as cereal contaminants, and their co-consumption is associated with liver cancer. Both are immunotoxic, but their interactions have been little studied. This work was aimed to evaluate in mouse spleen mononuclear cells (SMC) the effects of the exposure to AFB1 (5-50 µM), FB1 (25-250 µM), and AFB1-FB1 mixtures (MIX) on the in vitro differentiation of regulatory T cells (Treg and Tr1-like) and Th17 cells, as well as elucidate the contribution of aryl hydrocarbon receptor (Ahr) in such effects. AFB1 and mainly MIX induced cytotoxicity in activated CD4 cells via Ahr signaling. AFB1 (5 µM) increased the Treg cell differentiation, but its combination with FB1 (25 µM) also reduced Th17 cell expansion by Ahr-dependent mechanisms. Therefore, this mixture could enhance the Treg/Th17 cell ratio and favor immunosuppression and escape from tumor immunosurveillance to a greater extent than individual mycotoxins. Whereas, AFB1-FB1 mixtures at medium-high doses inhibited the Tr1-like cell expansion induced by the individual mycotoxins and affected Treg and Th17 cell differentiation in Ahr-independent and dependent manners, respectively, which could alter anti-inflammatory and Th17 immune responses. Moreover, individual FB1 altered regulatory T and Th17 cell development independently of Ahr. In conclusion, AFB1 and FB1 interact by modifying Ahr signaling, which is involved in the immunotoxicity as well as in the alteration of the differentiation of Treg, Tr1-like, and Th17 cells induced by AFB1-FB1 mixtures. Therefore, Ahr is implicated in the regulation of the anti- and pro-inflammatory responses caused by the combination of AFB1 and FB1.

Keywords: Aflatoxin B1; Aryl hydrocarbon receptor; Fumonisin B1; Immunotoxicity; Regulatory T cells; Th17 cells.

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References

    1. Abbès S, Ben Salah-Abbès J, Jebali R, Younes RB, Oueslati R (2016) Interaction of aflatoxin B1 and fumonisin B1 in mice causes immunotoxicity and oxidative stress: possible protective role using lactic acid bacteria. J Immunotoxicol 13(1):46–54. https://doi.org/10.3109/1547691X.2014.997905 - DOI
    1. Adeyemo BT, Enefe NG, Kayode TB et al (2022) Effects of dietary lanthanum chloride on growth performance, hematology and serum biochemistry of juvenile Clarias gariepinus catfish fed diets amended with mixtures of aflatoxin B1 and fumonisin B1. Toxins 14(8):553. https://doi.org/10.3390/toxins14080553 - DOI
    1. Ambrosio LF, Volpini X, Quiroz JN, Brugo MB, Knubel CP, Herrera MR, Fozzatti L, Avila Pacheco J, Clish CB, Takenaka MC, Beloscar J, Theumer MG, Quintana FJ, Perez AR, Motrán CC (2024) Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease. Front Immunol 14:1267641. https://doi.org/10.3389/fimmu.2023.1267641 - DOI
    1. Ambrosio LF (2019) Infección por trypanosoma cruzi : participación del receptor para aril hidrocarburos (AhR) en la regulación de la respuesta inmune. Tesis de Doctorado, Universidad Nacional de Córdoba. https://rdu.unc.edu.ar/handle/11086/15262 . Accessed Dec 2020
    1. Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ, Sherr DH, Weiner HL, Kuchroo VK (2010) The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol 11(9):854–861. https://doi.org/10.1038/ni.1912 - DOI

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